Carcinogenesis, Vol 18, 2127-2132, Copyright © 1997 by Oxford University Press
DJ Hunter, SE Hankinson, H Hough, DM Gertig, M Garcia-Closas, D Spiegelman, JE Manson, GA Colditz, WC Willett, FE Speizer and K Kelsey
Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants of
the rate of metabolic activation of carcinogenic compounds such as aryl
aromatic amines. Homozygosity for any combination of three variant alleles
in Caucasians defines 'slow' acetylators; presence of one or two wild-type
alleles characterizes 'rapid' acetylators. Although most previous studies
have not observed an overall elevation in risk of breast cancer among slow
acetylators, a recent study observed that cigarette smoking was associated
with a large increase in risk of breast cancer among slow acetylators. We
assessed the relation between NAT2 acetylation status and breast cancer
risk, and its interaction with smoking, in a prospective study of mainly
Caucasian US women. Four hundred and sixty-six incident cases who were
diagnosed with breast cancer after giving a blood specimen in 1989-90 were
matched to 466 controls in a nested case-control study. NAT2 genotype was
determined using PCR-RFLP assays. The multivariate relative risk (RR)
comparing slow with rapid acetylators was 0.9 (95% CI 0.7-1.2). Among slow
acetylators, current smoking immediately prior to diagnosis was not
associated with a significant elevation in risk compared with never smoking
rapid acetylators (RR = 1.4, 95% CI 0.7-2.6). No significant association
was seen between pack-years of smoking and risk of breast cancer among
either slow or fast acetylators. A non-significant elevation in risk was
observed among women who smoked for > or = 5 years prior to first
pregnancy and were rapid acetylators, compared with never smoking rapid
acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706
post-menopausal women, the elevated risks for current smokers immediately
prior to diagnosis who were slow acetylators compared with never smokers
who were fast acetylators were slightly stronger but still not
statistically significant. In summary, we observed little evidence of an
association between NAT2 genotype and breast cancer. In this prospective
study, cigarette smoking was not appreciably associated with breast cancer
among either slow or fast NAT2 acetylators.
ARTICLES
A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
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